There is an urgent need for a vaccine that will protect from infection with hepatitis C virus (HCV), which is a leading cause of liver cirrhosis and liver cancer. At present no such vaccine exists, and HCV infection is a major global public health problem. One of the obstacles to vaccine development is the high genetic diversity of the viral envelope glycoproteins.
HCV vaccine development has been thwarted by the high genetic diversity of the envelope glycoproteins and the presence of immunodominant, hypervariable regions within them. To elicit protective antibodies, the immune response needs to be focused on conserved, functionally important regions. The epitopes of broadly neutralizing antibodies (bnAbs) are therefore attractive leads for vaccine design.
One such bnAb is known antibody AP33, which binds to a conserved linear epitope (residues 412-423) on the HCV E2 envelope glycoprotein and potently neutralizes all genotypes of HCV.
The AP33 epitope, which spans residues 412 to 423 of HCV E2, is linear and highly conserved and encompasses a tryptophan residue that plays a critical role in CD81 recognition. The antibody has been shown to be capable of neutralising HCV across all the major genotypes. The rational development of immunogens that might mimic such epitopes and elicit AP33-like antibodies has been stymied by a range of factors in the art including the lack of detailed structural information available for the viral glycoproteins. Moreover, vaccination with peptides representing the epitope did not elicit antibodies that recognise E2.
It is a problem in the art to elicit antibodies that recognise E2.
The present invention seeks to overcome problem(s) associated with the prior art.